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Chi Zhang, Akina Hoshino, Thomas A Reh, Rachel O.L. Wong, Dennis M. Dacey; Development of the midget connectome of the human fovea. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2586.
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The midget circuitry in the human fovea shows a unique ‘private-line’ design, which enables high-resolution sampling of the visual scene. Each midget ganglion cell (GC) is contacted by one ON or OFF midget bipolar cell (BC) that receives input from a single cone photoreceptor. It is unclear how such precise connectivity is established during foveal development. One hypothesis is that the private-line forms at the onset of synaptogenesis, and is maintained throughout maturation. Alternatively, the foveal midget circuitry may undergo structural refinement to attain the ‘private-line’ arrangement. We tested these hypotheses by determining the connectivity of midget BCs and GCs in the fetal human retina from early- to mid-gestation when synaptogenesis is known to occur in the fovea.
The ultrastructure of the fovea in fetal human retinas (fetal weeks, Fwk14, 15 and 18 (1 retina each)) were obtained using serial block-face scanning electron microscopy. Three-dimensional reconstructions of cones, BCs, GCs and their synaptic connections were obtained using TrakEM.
ON and OFF midget-like BCs and GCs were identified at Fwk14 by the morphology and stratification of their arbors. Ribbon synapses were observed in both the inner and outer retina at this stage. As early as Fwk15, OFF midget BCs already contacted only a single cone. In contrast, although each ON midget BC largely synapsed with a cone, many also contacted at least one other neighboring cone. Cone convergence was still observed for ON midget BCs by Fwk18. The earlier establishment of the private-line between cones and OFF BCs compared to ON BCs is not reflected in the development of BC-GC connectivity. At Fwk14, both ON and OFF midget GCs received convergent BC contacts. Thereafter, by Fwk18, an ON midget GC was innervated largely by a single ON midget BC. But, OFF midget GCs at this stage were still innervated by multiple BCs, and each OFF midget BC distributed its synapses across several GCs, suggesting that further refinement has yet to occur in the OFF BC-GC circuitry.
Our reconstructions suggest that the basic circuit organization, such as synaptic contact with major partners and arrangement into ON and OFF connections, is present in the fovea by mid-gestation. Both synapse formation and elimination are, however, required to shape the private-line of foveal midget circuits. Moreover, ON and OFF midget circuits differ in their patterns of maturation.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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